What is the difference between lactulose and polyethylene glycol (Miralax) for the prevention of Hepatic Encephalopathy (HE)?

From the Guidelines

Lactulose is generally preferred over Miralax (polyethylene glycol) for preventing hepatic encephalopathy (HE). Lactulose is the first-line treatment for HE prevention, as it reduces ammonia production and absorption in the gut, with a typical dosage of 20-30 g taken orally 3-4 times daily, adjusted to produce 2-3 soft stools per day 1. While Miralax can also be used, it's considered less effective for HE prevention, primarily acting as an osmotic laxative without the specific ammonia-reducing effects of lactulose. Some key points to consider:

• Lactulose has a long history of use and more evidence supporting its efficacy in HE 1
• Lactulose reduces ammonia production by acidifying the colon and altering gut bacteria to favor non-ammonia producing species 1
• If a patient cannot tolerate lactulose due to taste or side effects, Miralax can be considered as an alternative, but it should not be the first choice for HE prevention 1 Some important considerations for treatment:
• The dosage of lactulose should be titrated to achieve two to three soft stools per day 1
• Patients should be monitored for symptoms of HE and have their dosage adjusted as needed 1
• Proper hydration and adherence to the prescribed regimen are crucial for effective prevention of HE 1

From the Research

Difference between Lactulose and Polyethylene Glycol (Miralax) for the Prevention of Hepatic Encephalopathy (HE)

• Lactulose is considered the first-line therapeutic agent for treating hepatic encephalopathy, as it is effective in minimal, overt, and recurrent hepatic encephalopathy 2, 3.
• Polyethylene glycol (PEG) has been compared to lactulose in the treatment of HE, with studies showing that PEG leads to a higher drop in the HE Scoring Algorithm (HESA) Score and thus leads to a faster resolution of HE compared to lactulose 4.
• A systematic review and meta-analysis found that PEG was superior to lactulose in reducing the average HESA Score at 24 hours, with a mean difference of -0.68 (95% CI -1.05 to -0.31) 4.
• Another study found that lactulose was effective in preventing the recurrence of HE in patients with cirrhosis, with a significant reduction in the development of overt HE compared to placebo 5.
• A network meta-analysis found that the combination of lactulose and rifaximin was the most effective treatment option for reducing the incidence of overt HE, followed by rifaximin and L-carnitine, and then lactulose and rifaximin with zinc 6.

Key Findings

• Lactulose is the standard of care for the treatment of HE, but PEG may be a viable alternative with faster resolution of HE 4.
• The combination of lactulose and rifaximin may be the most effective treatment option for reducing the incidence of overt HE 6.
• Lactulose is effective in preventing the recurrence of HE in patients with cirrhosis 5.
• PEG leads to a higher drop in the HESA Score compared to lactulose, resulting in faster resolution of HE 4.

Treatment Options

• Lactulose: effective in minimal, overt, and recurrent HE, and prevents recurrence of HE in patients with cirrhosis 2, 3, 5.
• Polyethylene glycol (PEG): leads to faster resolution of HE compared to lactulose, with a higher drop in the HESA Score 4.
• Rifaximin: equally effective as lactulose in managing HE, and better tolerated 2, 3.
• Combination therapies: lactulose and rifaximin, rifaximin and L-carnitine, and lactulose and rifaximin with zinc may be effective treatment options for reducing the incidence of overt HE 6.